CD14 is a known glycoprotein expressed on the membrane surface of monocytic cells and functions as a receptor of LPS (lipopolysaccharide). There are 2 types of CD14 molecules. One type is the membrane binding-type CD14 (mCD14) expressed on the cell surface. Another type is soluble CD14 (sCD14). sCD14s that have a molecular weight of about 55 kDa to about 49 kDa (hereinafter, referred to as the “high molecular weight sCD14”) are known in the art and these sCD14s are reported to show a high value in the blood of a patient with many diseases such as sepsis, acquired immune deficiency syndrome (AIDS), acute respiratory distress syndrome (ARDS) and systemic lupus erythematosus (SLE). For that reason, these high molecular weight sCD14s are not considered as disease-specific markers. See Hayashi, et al., Infection and Immunity, 67: 417-420, 1999; and Lawn, et al., Clinical & Experimental Immunology, 120: 483-487, 2000.
On the other hand, it has been reported that there is a new molecular species of sCD14, sCD14-ST (soluble CD14 antigen subtype, also referred to as presepsin), whose blood concentration is characteristically increased in sepsis patients.
sCD14-ST (presepsin) is characterized by being migrated to 13±2 kDa of the molecular weight in SDS-PAGE under non-reduction conditions of all sCD14s, and it comprises the N terminal part of CD14. sCD14-ST (presepsin) has an amino acid sequence in which the C terminal side is largely deleted compared to the amino acid sequences of high molecular weight sCD14, and unlike the high molecular weight sCD14, sCD14-ST (presepsin) does not have LPS binding ability. In addition, presepsin shows different immunogenicity from that of the high molecular weight sCD14, and therefore the molecules can be distinguished using the antibody. The blood concentration of presepsin specifically increases in sepsis patients (see WO 2005/108429 A1). Moreover, it is reported that the blood concentration of presepsin shows a higher value in the blood of sepsis patients compared to patients with systemic inflammatory response syndrome (SIRS), which is difficult to discriminate from sepsis. Thus, presepsin is considered a specific diagnosis marker of sepsis (Yaegashi, et al., Journal of Infection and Chemotherapy, 11: 234-238, 2005).
A rabbit-derived polyclonal antibody (S68 antibody) and a rat-derived monoclonal antibody (F1146-17-2), which specifically recognized presepsin, have been disclosed (see WO 2005/108429 A1 and WO 2004/044005 A1).
Presently, a measurement system using a rabbit-derived polyclonal antibody as a specific antibody to presepsin is practically used in the measurement of presepsin, and measurement kits to carry out the measurement system are on the market in Europe and Japan (PATHFAST™ Presepsin, Mitsubishi Chemical Medience Corporation).
Acquisition of an anti-human presepsin monoclonal antibody that can be practically used has been attempted, but an antibody having satisfactory performances has not been obtained.